Tuesday, December 11, 2018

Homocysteine and its Negative Impact on Bone

Elevated levels of homocysteine (Hcy) in the blood, a condition called hyperhomocysteinemia, is a common finding in patients with osteoporosis. Unfortunately, this not only increases a person's risk for fracture (by Hcy's adverse effects on bone quality), but for each 5 micromole/liter rise in Hcy, there is a 33.6% increase in all-cause mortality risk (Fan et al., 2017). 
Homocysteine is a byproduct from the metabolism of methionine, an amino acid found in meat (and nuts, soy, eggs, dairy). But even vegetarians can have elevated Hcy levels. This is because B12, a vitamin found in meat, is important for the conversion of Hcy into methionine and other metabolites. In addition to vitamin B12, several enzymes and the cofactors B2, B6, folate, betaine and magnesium are necessary to metabolize Hcy and lower its level in the blood. In cases of nutrient deficiency, and/or having the genetic polymorphism of the methylenetetrahydrofolate reductase (MTHFR) enzyme, Hcy levels rise and create breeding grounds for chronic disease.   
Homocysteine levels above 15 micromoles/liter can damage nerve cells and blood vessels leading to cognitive decline and cardiovascular insufficiency (Ostrakhovitch, 2018). In addition, hyperhomocysteinemia reduces bone strength by slowing osteoblastic bone-building activity, stimulating osteoclastic bone resorption, and disrupting bone collagen cross-linking molecules making collagen stiff and bones extremely fragile. Hcy creates oxidative stress in the body and increases the production of advanced glycation end products (AGEs) which reduces both bone quantity and quality and, therefore, bone strength.  
One of my goals, when helping patients reduce fracture risk, is to stop rapid bone loss and falling bone density T-scores. Through serial assessment of bone resorption biomarkers (CTX, NTX, and/or DPD) we are able to identify rogue osteoclastic activity and provide safe, appropriate, and effective therapy. Hyperhomocysteinemia can be effectively treated through exercise, diet, and nutritional supplementation. By lowering Hcy levels, we are able to see improvements in bone health through the lowering of bone resorption biomarkers.            
Fan, R. et al. 2017. Association between homocysteine levels and all-cause mortality: a dose-response meta-analysis of prospective studies. Scientific Reports 7, 4769.  
Ostrakhovitch E.A. and S. Tabibzadeh. 2018. Homocysteine and age-associated disorders. Ageing Research Reviews, https://doi.org/10.1016/j.arr.2018.10.010.  
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